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Stabilin‐1 protects against adverse inflammation and injury during viral myocarditis
Author(s) -
Papageorgiou Anna-Pia,
Carai Paolo,
Verhesen Wouter,
Velthuis Sebastiaan,
Lutgens Ester,
Rooijen Nico,
Swinnen Melissa,
Kzhyshkowska Julia,
Carmeliet Peter,
Heymans Stephane
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.680.21
Subject(s) - inflammation , myocarditis , wild type , biology , infiltration (hvac) , immunology , pathology , medicine , mutant , biochemistry , physics , gene , thermodynamics
Stabilin‐1 is a transmembrane glycoprotein expressed on activated macrophages and endothelial cells of new capillaries during tissue remodeling. In the coxsackie B3 (CVB3) murine model of viral myocarditis, stabilin‐1 expression increased significantly and was primarily expressed in macrophages. This was also seen in endomyocardial biopsies from patients with fulminant myocarditis, where stabilin‐1 was expressed by CD‐68+ macrophages, forming a protective barrier around the healthy tissue. When challenged with the CVB3 virus, Stabilin‐1 null mice showed increased cardiac related mortality as compared to wild‐type mice (p<0,001, n=19). Histological analysis showed that the stabilin‐1 null mice had increased cardiac necrosis due to CD3+ T‐lymphocyte infiltration, and lower F4/80+ macrophages as compared to their wild‐type littermates, suggesting that stabilin‐1 may be important for monocytes recruitment. Thioglycolate induced peritonitis in stabilin‐1 WT and null mice also resulted in fewer monocytes recruited. Depletion of circulating monocytes with clodronate liposomes in wild‐type mice induced a similar phenotype after CVB3 infection. We identify stabilin‐1 as an important upregulated protein during VM in both mice and humans and that absence of stabilin‐1 results in increased cardiac inflammation, injury and mortality, demonstrating a novel cardio‐protective effect of stabilin‐1.